Dialkyl substituted 2, 3-epoxyacid esters



United States Patent DIALKYL SUBSTITUTED 2,3-EPOXYACID ESTERS JosephLevy, Paramus, and Robert M. Lusskin, Haworth, N.J., assignors to TheTrubek Laboratories, East Rutherford, N .J a corporation of New JerseyNo Drawing. Application July 2, 1956 Serial No. 595,095

6 Claims. (Cl. 260-348) This invention relates to aliphatic saturatedbeta, beta-dialkyl substituted-2,3-epoxyacid esters or glycidic acidesters and to methods of producing the same.

In our copending application Serial No. 595,059, filed July 2, 1956, nowabandoned, we have described new alkyl poly-substituted aldehydes, andin accordance with a preferred method described therein for producingsuch aldehydes, saturated beta, beta-dialkyl substituted-2,3- epoxyacidesters may be produced as intermediate products. These intermediateproducts are themselves new compounds which further have been found topossess characteristic odors rendering them suitable for use inproducing perfumes or perfumed products and as flavoring agents.

-While it is well known that glycidates containing aromatic substituentspossess odors rendering them useful in perfumes and flavoringcompositions, 2,3-epoxyacid esters or glycidates containing only alkylsubstituents have not previously been noted to possess suchcharacteristics to a pronounced degree. It now appears that whenaliphatic glycidic acid esters are dialkyl substituted in the betaposition and one of the alkyl groups is a branched chain alkyl so thatthe compound is an ester of a saturated 3,4-dialkylsubstituted-2,3-epoxyacid, the product will have pronounced odor andflavoring prop erties. Therefore, the preferred compounds of the presentinvention may be said to have the composition indicated by the followingformula:

wherein R, R' and R" are saturated alkyl radicals and R'" may be asaturated or unsaturated radical.

The principal object of the present invention is to provide a new classof odor and flavoring agents consisting of aliphatic saturated beta,beta-dialkyl-substituted- 2,3-epoxyacid esters. I

Another object of the invention methods for producing'such esters.

A particular object of the invention is to provide esters of aliphaticsaturated 3,4-dialkyl substituted-2,3- epoxyacids which may be employedin the production of perfumes, perfumed products and flavoring agents.

These and other objects and features of the present invention willappear from the following description thereof in which reference is madeto particular compounds and procedures for the purpose of indicating thenature and character of the invention but without intending to limit theinvention thereby.

The compounds of the present invention vary considerably in odor in thatsome possess a fruity odor, others have a berry-like odor, while stillothers have what may be described as an herby odor. The particular odordeveloped in any compound will depend largely upon the nature andlocation of the various aliphatic radicals.

is to provide novel The alkyl groups which may be present in thecompounds can be varied greatly. Among those groups which may be presentare methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl,heptyl and the like as well as their various branch chain isomers. Ingeneral, the alkyl groups present in the most important members of theseries contain from 1 to 4 carbon atoms. When longer alkyl groups arepresent in the compound, the product is generally less volatile andtherefore has a weaker odor or one which is less significant. However,such higher alkyl compounds may be used as blending or odor modifyingagents or as additives for use with perfumes or perfumed products.

A further important characteristic of the compounds of the presentinvention resides in their stability in the presence of soap. Thus, whenmixed with soaps, they do not cause discoloration or rancidity andtherefore are particularly useful for perfuming soaps.

Compounds of the present invention may be prepared by reacting anappropriately alpha-substituted aliphatic ketone, containing, say 6 to11 carbon atoms, with an ester of chloracetic acid or bromacetic acid inthe presence of an alkaline condensing agent such as sodium, sodiummethylate or other sodium alkoxide, sodamide, or the like. The reactionmay be represented by the following general equation:

If the alkyl group of the sodium alkoxide or other condensing agent useddiffers from the alkyl group of the chloracetic ester (that is if the Rand R" of the foregoing equation are different), the epoxyacid estersproduced will be mixed esters. Such mixtures of esters may be separatedby fractional distillation or other methods, if desired, or the mixturesof esters may be used as a blend wherein the differently odored esterscombine to produce a distinctive new effect.

When desired a lower aliphatic ester of the epoxyacid may be convertedinto a higher aliphatic ester by alcoholysis, as by heating the lowerester with a higher alcohol in the presence of a catalyst such assodium, anhydrous sodium methylate or the like.

The aliphatic ketones required in producing many of the products of thepresent invention are not commercially available, but they may beproduced by condensing an aliphatic aldehyde with an aliphatic ketonecontaining at least four carbon atoms to obtain an alpha substitutedbeta-hydroxyketone. Various aldehydes and ketones may be selected asstarting agents depending upon the nature of the particular end productto be obtained. Among the aldehydes which may be used are acetaldehyde,propanal, butanal, isobutanal, pentanal, heptanal, octanal, decanal andtheir various branched chain isomers. Similarly among the ketones whichmay be used are methyl ethyl ketone, diethyl ketone, dibutyl ketone,methyl propyl ketone, methyl amyl ketone, methyl nonyl ketone, and thelike. If desired, unsaturated aldehydes and ketones may be used.

The selected aldehyde and ketone required for producing any desired endproduct are condensed and dehydrated to produce an alpha substitutedunsaturated ketone. In the preferred practice of the invention, thestarting materials employed are alkylaldehydes and dialkyl ketonesselected to produce an alpha-substituted, alpha, beta unsaturated ketoneupon condensation. The general equa tion' for such a reaction is asfollows:

Either alkaline or acid condensing agents may be usedand in general, thealkaline agents are preferred. Thus, sodium hydroxide; potassiumhydroxide, barium hydroxide, hydrochloric acid, zinc chloride, or thelike may be used. However, if R is such that the aldehyde has a branchedchain inthe alpha position and R" of the ketone is methyl, an acidcondensing agent is preferred in order to assure attack of the aldehydeupon the methylene group of the ketone.

The alpha-substituted unsaturated ketone obtained by such condensationis thereafter hydrogenated to the alpha substituted saturated ketone andthe latter then converted into an ester of a beta,beta-disubstituted-Z,3-epoxy or glycidic acid. For this purpose thealpha-substituted saturated ketone is preferably reacted with an esterof chloracetic acid or bromacetic acid in the presence of an alkalinecondensing agent such as sodium, sodium methylate or other sodiumalkoxides, sodamide, or the like. The reaction proceeds as representedby the following, equation:

In order to illustrate typical procedures which may be employed in thepractice of the present invention, the following examples are cited.

Example I 968 gms. of acetaldehyde were added with stirring at -5 C. in6 hrs. to a mixture of 4752 gms. methyl ethyl ketone and 33.6 gms.potassium hydroxide dissolved in 166 gms. methanol. After stirring for 1hr. at 0-5 40 gms. oxalic acid was added and the precipitated potassiumoxalate removed by filtration. The unreactedmethyl ethyl ketone was thendistilled out to 94 C. (pot temp.=l56). After cooling to 100 C., anadditional 40 gms. oxalic acid was added and the mixture again distilledto give 2080 gms. crude product (plus some water) distilling from 80170C. The water was separated and the product redistilled to give 1276 gms.3-methyl-3- pentene-Z-one distilling at 137-142" C.

1224 gms. of the 3-methyl-3-pentene-2-one thus obtained was charged intoan autoclave with 24.5 gms. of 5% palladium-charcoal catalyst andhydrogenated at about 25 and at a pressure of to 50 pounds per squareinch of hydrogen gas. Reduction of the carboncarbon double bondwascompleted in about 3 /2 hours after which absorption of hydrogenceased. The catalyst was removed by filtration and the product distilledto give about 96% yield of 3-methyl-pentanone-2. The pure compounddistilled at 121.

A mixture of 456 gms. 3-methylpentanone-2 and 793 gms. methylchloracetate was cooled to about 10 C. and 394 gms. anhydrous sodiummethylate added in-portions during 2 /2 hours with stirring and coolingso that the temperature did not rise above 0 C. Thetemperature was thengradually raised to about 25 during a period of 1 /2 hours and thenallowedto stand overnight. The mixture was then heated at reflux for 1hour, cooled to about 30 C. and treated with about 30 g. acetic aciduntil acid to litmus paper followed by 228 gms. water. The. oil layerwas separated and distilled. Unreacted ketone along with otherby-products were recovered in the? fraction distilling from 37-100 C. atmm. of pressure;- end; then 369.4 guts. of.methyl-3,4-dimethylr2,3-epoxy,-

hexanoate was obtained distilling at -85 at 5 mm. of pressure. Thiscompound has a mild berry-like odor and may be represented by theformula CH -GH;OHO OHCOOCH Example 11 A mixture of 77.5 gms.methyl-3,4-dimethyl-2,3-epoxyhexanoate, 133.3 gms. isobutyl alcohol, and2.1 g; anhydrous sodium methylate, as catalyst, were heated in afiaskfitted with a fractionating column while slowly distilling out methanolformed in the reaction. As the temperature of the mixture was graduallyraised from about 99 C. to about 131 C. duringa period of four hours,there was obtained gms. of distillate boiling from 67 to 108 C. andconsisting of a mixture of methanol and isobutanol. The material in theflask Was cooled to about 25"" C. and treated withabout 2.5 gms. aceticacid followed by 300 cc. saturated salt solution. The oil layer wasseparated and distilled giving 842 gms.isobutyl-3,4-dimetl1yl-2,3--epoxyhexanoate distilling at 123l24 C. at 10mm. of pressure. This compound has a mild herb-like odor and may berepresented by the formula 3-methylpentanone-2 was reacted with ethylchloracetate with anhydrous sodium methylate as the condensing agentaccording to the general procedure of Example I to give a mixture of themethyl and ethyl esters of 3,4-dimethyl-2,3-epoxyhexanoic acid'distilling at 118l24 C. at 20 mm. of pressure. The ethyl esterseparated. from this mixture has an odor reminiscentof raspberries but:difl'ering quite characteristically from that of the correspondingmethyl ester. formula OH -GH CHOCH-COOC H CH CH Example IV Following thegeneral procedures of Example I, acetaldehyde was reacted withdiethyl'ketone and the product dehydrated (with iodine instead of oxalicacid) to give 4-methyl-4-hexene-3-one (B.P.=l6l C.). Reductionof thedouble bondgave 4-methylhexanone-3 (B.P.= 135-8) and reaction of thisketone with ethyl chloracetate in the.

presence of anhydrous sodium methylate gave a mixture ofthe methyl plusethyl esters of 4-methyl-3-ethyl-2;3-- epoxyhexanoic acid (B.P.=-105 at5 mm: pressure);

The ethyl ester separated from this mixturahasa pungent:

It may be represented by the assasse herb-like odor. The compound may berepresented by the formula CHrCHrCHC CH-COOCHg-OH (3H H. an,

Example VI Following the general procedure of Example I, heptaldehydewas reacted with methyl ethyl ketone and the product dehydrated (withiodine instead of oxalic acid) to give 3-methyl-3-decene-2-onedistilling at 100-105 C. at 5 mm. pressure (Nd at 20=1.4545).Hydrogenation of this compound gave 3-methyldecanone-2 distilling at92-95 at 5 mm. pressure (Nd at 20=1.4280) and reaction with methylchloracetate in the presence of anhydrous sodium methylate gave thedesired methyl-3,4-dimethyl-2,3-epoxyundecanoate distilling at 1219 C.at 2 mm. pressure. This compound has no very significant odor in itself,but may be used as a blending agent or fixative in producing perfumes orperfumed products. It is represented by the formula 50 g. methyl3,4-dimethyl-2,3-epoxyhexanoate, 138.8 g. geraniol and 1.9 g. anhydroussodium methylate as catalyst were heated in vacuo at 100 C. in a flaskfitted with a fractionating column until methanol no longer was evolved.The excess geraniol was then distilled away from the mixture and aftercooling to about 25 the crude product was acidified with dilute aceticacid and extracted with benzene. After removal of the benzene theproduct was distilled in vacuo to give geranyl3,4-dimethyl-2,3-epoxyhexanoate distilling 141-2 at 0.6 mm. of pressure.This material had a weak and very mild odor, but may be used as ablending agent in perfumes and perfumed products. It may be representedby the formula may be varied over a wide range to produce compoundshaving quite different and distinctive odor and flavor 6characteristics. Furthermore, the compounds of the present invention maybe employed as indicated in our copending application Serial No.595,059, filed July 2, 1956, as intermediates in the production of newaldehydes and other compounds or products.

While numerous typical compounds of the series to which this inventionrelates have been specifically referred to or described above, andpreferred methods described for producing such compounds, it will beapparent that many other compounds embodying the present invention maybe produced. Moreover, it is pointed out that the odor of the compoundsvaries over a wide range in both character and intensity depending uponthe type, location and the relative positions of the varioussubstituents in the carbon chain as well as those of the ester group.Those compounds having relatively high boiling points ordinarily possessless odor and accordingly, compounds containing no more than about 20carbon atoms are preferred for most purposes. However, even the higherboiling compounds and those containing more than 20 carbon atoms may beused as blending agents or modifiers in perfumes and perfumed products.

It will also be evident that the ketones used in the preferred methodsof procedure described may be produced or obtained in any suitable wayand it is possible that the epoxyacid esters themselves may be producedby methods other than those herein described.

In view thereof it should be understood that the particular compoundsreferred to above and the methods for their production described in thevarious examples cited have been chosen for the purpose of indicatingthe general nature of the invention and are not intended to limit thescope thereof.

We claim:

1. A lower alkyl ester of 3,4-dimethy1-2,3-epoxyhexanoic acid.

2. Methyl-3,4-dimethyl-2,3-epoxyhexanoate.

3. Ethyl-3,4-dimethyl-2,3-epoxyhexanoate.

4. Isobutyl-3,4-dimethyl-2,3-epoxyhexanoate.

5. Methyl-3-methy1-4-ethyl-2,3-epoxyhexanoate.

6. Methyl-4-methyl-3-ethyl-2,3-epoxyhexanoate.

References Cited in the file of this patent UNITED STATES PATENTS1,873,430 Knorr Aug. 23, 1932 1,899,340 Knorr Feb. v28, 1933 2,680,109Stevens June 1, 1954 OTHER REFERENCES Beilstein, vol. #17-19, 1st supp.,p. 436 (1934). Beilstein, vol. 18, p. 263 (1952).

1. A LOWER ALKYL ESTER OF 3,4-DIMETHYL-2,3-EPOXYHEXANOIC ACID.